Parallel en-face optical coherence microscopy with adaptive focus Abstract. We propose a novel parallel nonstralational optical coherence microscopy (OCM) with adaptive focus for general high-speed high-resolution en-face biomedical imaging. Optical coherence tomography (OCT) has become an emerging imaging modality with high depth resolution. OCM is one kind of OCT imaging technique with better transverse and depth resolution by using confocal architecture in the object arm. Typical OCT systems generate B- scan cross section images. In clinic, the users are more familiar with C-scan (en face) images. Parallel OCT imaging has been studied, but not in the OCM architecture. Furthermore, in the conventional OCT/OCM imaging, good transverse resolution can be maintained only in the region close to the focal plane. Dynamic focusing can only be done by mechanic movement. To overcome these problems, here we propose to demonstrate, for the first time, a nontranslational parallel en-face OCM imaging instrument with adaptive focus. A programmable digital micromirror device is used for parallel confocal sampling, an electro-optic varifocal lens for fast depth scanning, and a rapid CMOS camera with more than 1000 frames/s rate for data collection. With adaptive focusing, the transverse resolution is constant across the depth of imaging. The spatial resolution can be around 2 <m W 2 <m W 4.5 <m in three dimensions. The imaging depth is higher than that of the confocal or full-field OCT imaging alone. With the rapid speed of the digital micromirror device (microsecond), the vafifocal lens, and the CMOS camera, the data acquisition speed is very high (volume/s). The pixel dwell time is increased. It allows lower excitation laser power and higher sensitivity. The signal-to-noise ratio would be higher than other full-field OCT imaging without confocal architecture. Since in the object arm, both longitudinal and transverse scanning are performed electro- optically without translational components, the moving effect of the sample due to mechanic vibration of the conventional imaging system can be avoided. The instrument provides a new tool to assess tissue and cell function and morphology in real time. In the proposed exploratory phase of this technology-driven project, we will perform experiments on general biologic relevant samples to demonstrate the functionality of the system. These samples include tissue phantoms based on gelatin embedded micro spheres covering a USAF 1951 target, onion skin, and tadpole. Images from biological samples will be compared to published OCT images and microscopy images of our corresponding thin sectioned samples. Pilot study of application of this imaging system for diagnosis of cornea disease will be performed too. PUBLIC HEALTH RELEVANCE (provided by the applicant): We have proposed a novel parallel nonstralational optical coherence microscopy (OCM) with adaptive focus for general high-speed high-resolution en-face biomedical imaging. Our research proposal currently focuses on demonstration the feasibility of this new technique. With adaptive focusing, the transverse resolution is constant across the depth of imaging. [The spatial resolution can be around 2<m 4 2<m 4 4.5<m in three dimensions. The imaging depth is higher than that of the confocal or full-field OCT imaging alone. With the rapid speed of the digital micromirror device (microsecond), the varifocal lens, and the CMOS camera, the data acquisition speed is very high (~1190 frames/s or higher).It allows higher sensitivity. The signal-to-noise ratio would be higher than other full-field OCT imaging without confocal architecture. Since in the object arm, both longitudinal and transverse scannings are performed electro-optically without translational components, the moving effect of the sample due to mechanic vibration of the conventional imaging system can be avoided. The instrument provides a new tool to assess tissue and cell function and morphology in real time. The potential applications include general cell imaging, visualizing epithelial tissue layers or structures of the eye (cornea). Miniaturization and portability of the system will be considered in the future. Model system for epithelial tissue would be fresh samples of colon and cheek with the goal to image individual cells in epithelial tissues down to the basement membrane. This would demonstrate potential application in colon cancer screening and oral cancer screening. For eye imaging, such a system can be used for diagnosis of the ocular surface diseases.